Anti-DFS70 Antibodies Among Patient and Healthy Population Cohorts in China: Results From a Multicenter Training Program Showing Spontaneous Abortion and Pediatric Systemic Autoimmune Rheumatic Diseases Are Common in Anti-DFS70 Positive Patients

Abstract

Objective Anti-DFS70 antibodies correlating with the nuclear dense fine speckled (DFS) pattern in the HEp-2 indirect immunofluorescence assay (IFA) are less common in patients with systemic autoimmune rheumatic disease (SARD) than in healthy subjects and their clinical associations remain elusive. We hosted a multi-center HEp-2 IFA training program to improve the ability of clinical laboratories to recognize the DFS pattern and to investigate the prevalence and relevance of anti-DFS70 antibodies. Methods DFS pattern sera identified by HEp-2 IFA in 29 centers in China were redirected to a central laboratory for anti-DFS70 testing by line immunoblot assay (LIA), enzyme-linked immunosorbent assay (ELISA), and IFA with HEp-2 ELITE/DFS70-KO substrate. Anti-extractable nuclear antigen antibodies were measured by LIA and the clinical relevance was examined in adult and pediatric patients. Results HEp-2 IFA positive rate and DFS pattern in positive sera were 36.2% (34,417/95,131) and 1.7% (582/34,417) in the patient cohort, and 10.0% (423/4,234) and 7.8% (33/423) in a healthy population, respectively. Anti-DFS70 prevalence among sera presenting the DFS pattern was 96.0, 93.7, and 49.6% by ELISA, LIA, and HEp-2 ELITE, respectively. 15.5% (52/336) of adult and 50.0% (20/40) of pediatric anti-DFS70 positive patients were diagnosed with SARD. Diseases most common in anti-DFS70 positive patients were spontaneous abortion (28.0%) in adults and juvenile idiopathic arthritis (22.5%) in pediatric patients. Conclusion Accurate DFS pattern identification increased the detection rate of anti-DFS70 antibodies by ELISA and LIA. Anti-DFS70 antibodies are remarkably high in cases of spontaneous abortion and in pediatric SARD patients, but not prevalent in adult SARD patients.

Dense fine speckled immunofluorescence pattern in a Chinese population: Prevalence and clinical association

“…In this study, a total of 36,869 patients who had positive ANA IIF test results were enrolled, and among them, patients with the DFS pattern accounted for 1.27%. Similar result (1.7%) was found in a study that included patients from 30 hospitals and 14 provinces across China 18 . By comparison, a study from Australia showed a higher frequency (5.7%), 19 which could be explained by differences in prevalence of the DFS pattern, races, etc.…”

Antinuclear Autoantibodies in Health: Autoimmunity Is Not a Synonym of Autoimmune Disease

“…However, recent findings raise some questions regarding the clinical relevance of anti-DFS70 autoantibodies. Zheng et al showed that the frequency of systemic autoimmune rheumatic diseases in anti-DFS70 positive pediatric patients was unexpectedly as high as 50.0% [ 59 ]. Conticini et al reported that 7/9 (77.8%) anti-DFS70 positive adult patients with clinical suspicion of primary Sjogren syndrome received this diagnosis after minor salivary gland biopsy [ 60 ].…”

Anti-DFS70 Antibodies for Differentiating Systemic Autoimmune Rheumatic Disease in Patients with Positive ANA Tests: A Systematic Review and Meta-Analysis

“…However, a recent meta-analysis focusing on the diagnostic performance of anti-DFS70 antibodies among patients presenting with a DFS pattern in an ANA test found substantial heterogeneity in both the sensitivity and specificity [ 15 ]. The difficulty in recognizing the DFS pattern [ 16 , 17 , 18 ] and the presence of other autoantibodies that produce a DFS pattern in ANA tests [ 19 , 20 ] may not only contribute to the heterogeneity but also hinder the application of the study results to clinical practice. In contrast, although heterogeneity still exists, the identification of a positive ANA test may be more widely adopted and validated in laboratories worldwide than a DFS pattern [ 16 , 17 , 18 ].…”

“…The difficulty in recognizing the DFS pattern [ 16 , 17 , 18 ] and the presence of other autoantibodies that produce a DFS pattern in ANA tests [ 19 , 20 ] may not only contribute to the heterogeneity but also hinder the application of the study results to clinical practice. In contrast, although heterogeneity still exists, the identification of a positive ANA test may be more widely adopted and validated in laboratories worldwide than a DFS pattern [ 16 , 17 , 18 ]. Therefore, focusing on studies enrolling patients presenting with a positive ANA test, rather than a DFS pattern, for meta-analysis may decrease the heterogeneity between studies and increase the applicability of their results.…”